Nanoemulsions have become ideal candidates for loading hydrophobic active ingredients and enhancing their bioavailability in the pharmaceutical, food, and cosmetic industries. However, the lack of versatile carrier platforms for nanoemulsions hinders advanced control over their release behavior. In this work, a method is developed to encapsulate nanoemulsions in alginate capsules for the controlled delivery of lipophilic active ingredients. Functional nanoemulsions loaded with active ingredients and calcium ions are first prepared, followed by encapsulation inside alginate shells. The intrinsically high viscosity of the nanoemulsions ensures the formation of spherical capsules and high encapsulation efficiency during the synthesis. Moreover, a facile approach is developed to measure the nanoemulsion release profile from capsules through UV-vis measurement without an additional extraction step. A quantitative analysis of the release profiles shows that the capsule systems possess a tunable, delayed-burst release. The encapsulation methodology is generalized to other active ingredients, oil phases, nanodroplet sizes, and chemically crosslinked inner hydrogel cores. Overall, the capsule systems provide promising platforms for various functional nanoemulsion formulations.

However, conventional oral drug formulations typically require costly multistep manufacturing, and poor bioavailability of hydrophobic APIs still remains a persistent challenge in many formulations. It has been reported that 40% of marketed drugs and 90% of drug candidates in the pipeline are hydrophobic. [4] Their poor water-solubility renders the drugs difficult to be absorbed in the gastrointestinal tract, greatly undermining their potency. Over the past decade, many attempts have been made to develop methods for producing API nanocrystals that possess improved solubility and bioavailability because of their significantly larger specific surface area compared to their bulk counterparts. [5][6][7] However, incorporation of the methods into conventional formulation processes is susceptible to many problems. For example, suitable excipients have to be investigated through tedious trial-anderror experiments, [8][9][10] and API inhomogeneity raises a potential risk that causes overdosed or ineffective treatment. [11] Methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) are two types of natural-based cellulose ester excipients that have been widely formulated into oral solid dosage forms in food and pharmaceutical applications. [12][13][14] Their unique swelling and erosion behaviors are suitable for the design of controlled release systems and for the study of drug delivery models. [15] Upon contact with water, a gel layer can form on the polymer surface due to rapid hydration, which slows down further water penetration into the inner dry polymer core. [16] In addition, fast release can be easily achieved with the use of MC which shows a much faster matrix erosion than HPMC. [14] Despite these ideal properties, formulations of these cellulose esters and hydrophobic APIs into drug products still lack efficient control over API nanocrystal sizes and heavily depend on multiple blending, sieving, and granulation steps. [17,18] Reversible thermal gelation is another "smart" property of MC and HPMC that has gained considerable attention in the field of rheology [19,20] and tissue engineering. [21,22] The polymer gels upon heating and returns back to the sol state upon subsequent cooling. [20] Although researchers have applied this property to develop in situ gelling materials for drug delivery, [23,24] the utility of the thermal gelation property Oral drug products have become indispensable in modern medicine because of their exceptional patient compliance. However, poor bioavailability of ubiquitous low-water-soluble active pharmaceutical ingredients (APIs) and lack of efficient oral drug formulations remain as significant challenges. Nanocrystalline formulations are an attractive route to increase API solubility, but typically require abrasive mechanical milling and several processing steps to create an oral dosage form. Using the dual amphiphilic and thermoresponsive properties of methylcellulose (MC), a new thermogelling nanoemulsion and a facile thermal dripping method are developed for efficient formulatio...

Oral thin films are an emerging solid dosage form for the delivery of poorly water-soluble drugs. Typical thin film formulations require nanomilling of drugs to improve their poor water solubility, followed by incorporating the drug nanoparticles in a polymer solution for casting. However, these formulations are not only inefficient and multistep but also limited to moderate drug loading capacity and susceptible to irreversible nanoparticle aggregation. Based on a widely used filmforming polymer, hydroxypropyl methylcellulose (HPMC), we developed thermogelling nanoemulsions with drug-loaded oil nanodroplets dispersed in a HPMC-loaded water phase. The nanoemulsions can directly act as film precursors for casting and provide robust templates to formulate oral films with uniform drug nanoparticles embedded in a dried HPMC matrix. The thermally gelled network effectively immobilizes the oil nanodroplets for confined nanoparticle crystallization and avoids potential irreversible nanoparticle aggregation, which enables high drug loading contents up to 63 wt %. The oral films also possess a tunable immediate release because the films have large surface-to-volume ratios and the drug nanoparticles are fast-dissolving. Overall, the thermogelling nanoemulsions show great promise for a more efficient and effective process to formulate HPMC and poorly water-soluble drugs into highly potent oral films with tunable immediate release.

Hydrophobic active pharmaceutical ingredients are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core‐shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core‐shell hydrogel particles.This article is protected by copyright. All rights reserved